The present invention relates to a novel hydroxyapatite that resembles a constituent of bones and can be used for various tissues such as artificial bones and medical materials, a complex having this hydroxyapatite, and a production method thereof. The present invention also relates to use of the hydroxyapatite or the complex in the manufacture of an artificial tissue and a medical material, utilizing the hydroxyapatite or the complex.
Main layers of tissues such as a bone and a tooth consist of inorganic solid substances that resemble hydroxyapatite (sometimes abbreviated hereinbelow as HAp). It is known that ceramic materials having biocompatibility can be used for fixing damaged bones and teeth. Known examples of such materials include xe2x80x9cBioglassxe2x80x9d (trade name, manufactured by Nippon Electric Glass Co. Ltd., Otsu. Siga. Japan, containing Na2Oxe2x80x94CaOxe2x80x94SiO2xe2x80x94PiO5), which is used mainly as a restorative material in dental surgery, a sintered compact of HAp (Ca10(PO4)6(OH)2) that is used mainly as a bone filling material, and a crystallized glass containing apatite and wollastonite (CaOxe2x80x94SiO2) (trade name xe2x80x9cCerabone A-Wxe2x80x9d, manufactured by Nippon Electric Glass Co. Ltd., Otsu. Siga. Japan) which is used for an artificial otoconite or an ilium spacer.
There have been made attempts to cover a surface of a material having high strength such as a metal with these ceramic materials for producing a bone substitute. Further, there has been developed a so-called biomimetic process, that is, a method for forming a HAp layer on a surface of various organic high molecular materials that can readily be processed, for application to production of artificial tissues other than bones that has flexibility and durability.
This biomimetic process is performed as follows: introducing glass particles containing as principal constituents CaO and SiO2 into an aqueous solution having the same ion concentration as that of human body fluid (simulated body fluid); immersing an organic high molecular material therein to have many apatite cores formed on the surface of the organic high molecular material; taking the organic high molecular material out of the simulated body fluid; and immersing the organic high molecular material in a solution having 1.5 times the ion concentration of the simulated body fluid. It is reported that, by this biomimetic process, the apatite cores grow naturally on the organic high molecular material to form a desired thickness of a bone-like HAp layer that is compact and homogeneous (J. Biomed.Mater.Res. vol.29, p349-357(1995)).
However, the rate of generation of HAp in this biomimetic process is so slow that even the long reaction time, such as more than two weeks, is not sufficient for obtaining the organic high molecular material having the HAp thereon that can be used as an artificial bone.
The aforementioned ceramic materials are required to have biocompatibility such that the materials can bind to live bones. Researches as to composition and configuration have been made to obtain such biocompatibility. Recently, it has been found out that the crystal structure of the ceramic materials is as important as the composition and the configuration thereof for improving biocompatibility. For example, it is known that the crystal structure of a human bone shows specific diffraction peaks shown in FIG. 10 in X-ray diffractometry (Biomaterials, 11, p568-572, 1990).
However, HAp having a crystal structure that resembles such a structure of the human bone is not hitherto known. For example, although the HAp obtained by the aforementioned biomimetic process is reported to be a bone-like HAp layer, it does not have such a crystal structure.
The first object of the present invention is to provide a novel hydroxyapatite having the composition and the crystal structure that resemble those of bones and exhibiting an excellent biocompatibility, and a production method thereof.
The second object of the present invention is to provide a method for producing a hydroxyapatite that can produce a hydroxyapatite having the composition and the crystal structure that resemble those of bones and exhibiting an excellent biocompatibility, in an extremely high production rate and efficiency.
The third object of the present invention is to provide a complex that has a hydroxyapatite having excellent biocompatibility and a bone-like crystal structure, and that is useful as a medical material, an artificial bone and various artificial tissues other than bones that are required to have flexibility, as well as a production method of such a complex.
The fourth object of the present invention is to provide a method for producing a complex by which a hydroxyapatite having excellent biocompatibility and a bone-like crystal structure can be produced in an extremely high rate and efficiency, and by which a complex useful as a medical material, an artificial bone and various artificial tissues other than bones that are required to have flexibility can readily be obtained.
The fifth object of the present invention is to provide a tissue such as an artificial bone having a hydroxyapatite that has the composition and the crystal structure which resemble these of bones, and that has excellent biocompatibility.
In developing a biocompatible material for an artificial bone and various tissues having flexibility and durability, the present inventors made extensive researches for production method of a novel hydroxyapatite that resembles inorganic solid substances constituting bones not only in the composition but also in the crystal structure. As a result, the present inventors found out that a novel hydroxyapatite which resembles bones in the crystal structure as well as the composition can be produced by alternately immersing a substrate such as an organic high molecular polymer or various metals in a solution containing calcium ions and substantially free of phosphate ions, and in another solution containing phosphate ions and substantially free of calcium ions, to complete the present invention.
That is, according to the present invention, there is provided a hydroxyapatite consisting essentially of Ca10(PO4)6(OH)2, and having a crystal structure that causes diffraction peaks at 31-32xc2x0 and 26xc2x0 in X-ray diffractometry (referred to hereinafter as xe2x80x9cHAp of the present inventionxe2x80x9d).
According to the present invention, there is also provided a method for producing the hydroxyapatite comprising the steps of (A) immersing a substrate in a first aqueous solution which contains calcium ions and is substantially free of phosphate ions and in a second solution which contains phosphate ions and is substantially free of calcium ions, to produce the HAp of the present invention at least on a surface of the substrate; and (B) recovering the HAp of the present invention from the substrate.
According to the present invention, there is further provided a complex having the HAp of the present invention at least on a surface of a substrate.
According to the present invention, there is further provided a method for producing the complex comprising the step of (A) immersing a substrate in a first aqueous solution which contains calcium ions and is substantially free of phosphate ions and a second solution which contains phosphate ions and is substantially free of calcium ions, to produce the HAp of the present invention at least on a surface of the substrate.
According to the present invention, there is further provided an artificial tissue consisting essentially of the HAp of the present invention or the complex.
According to the present invention, there is further provided use of the HAp of the present invention or the complex in the manufacture of a medical material.